Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases

Doortje W Dekens, Ulrich L M Eisel, Leonie Gouweleeuw, Regien G Schoemaker, Peter P De Deyn, Petrus J W Naudé*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

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Abstract

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2 expression is increased in the periphery and the brain in different age-related CNS diseases and also their risk factor conditions. Experimental studies indicate that Lcn2 contributes to various neuropathophysiological processes of age-related CNS diseases, including exacerbated neuroinflammation, cell death and iron dysregulation, which may negatively impact cognitive function. We hypothesize that increased Lcn2 levels as a result of age-related risk factor conditions may sensitize the brain and increase the risk to develop age-related CNS diseases. In this review we first provide a comprehensive overview of the known functions of Lcn2, and its effects in the CNS. Subsequently, this review explores Lcn2 as a potential (neuro)inflammatory link between different risk factor conditions and the development of age-related CNS disorders. Altogether, evidence convincingly indicates Lcn2 as a key constituent in ageing and age-related brain diseases.

Original languageEnglish
Pages (from-to)1-31
Number of pages31
JournalAgeing Research Reviews
Volume70
DOIs
Publication statusE-pub ahead of print - 26-Jul-2021

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